In young cattle, respiratory disease is treated primarily by the administration of long acting, injectable antimicrobials intended for single-dose administration. Interestingly, less than 60% of dairy producers consult their veterinarian for specific details about antibiotic usage and 85% use antibiotics in an extra label manner (USDA, 2018). High levels of disease, potential misuse, and retreatment rates contribute to the overall volume of antibiotics administered to dairy calves. This is costly and contributes to the selection pressure for antimicrobial resistance in both pathogenic and commensal bacteria. This is especially concerning because the three classes of antibiotics known for promoting antimicrobial resistance by selecting for multi-drug resistant bacteria in animals and people (third-generation cephalosporins, fluoroquinolones, and macrolides; Guardabassi et al., Reference Guardabassi, Apley, Olsen, Toutain, Weese, Frank, Stefan, Jianzhong and Lina2018) are administered to nearly 50% of calves treated for respiratory diseases (USDA 2018).

In the field setting, treatment response is either not measured at all, or is assessed indirectly at the herd level by looking at producer treatment records (e.g. retreatment rate and average number of treatments per calf). In the research setting, response is often gaged by clinical cure rate, clinical relapse rate, mortality rate, average daily gain, and severity of lung lesions at necropsy. Using criteria based largely on the resolution of clinical signs, most reports suggest that 20–35% of treated calves require multiple antibiotic treatments for relapse or recurrence of their respiratory disease (van Donkersgoed et al., Reference Van Donkersgoed, Ribble, Boyer and Townsend1993; Windeyer et al., Reference Windeyer, Leslie, Godden, Hodgins, Lissemore and LeBlanc2012; Heins et al., Reference Heins, Nydam, Woolums, Berghaus and Overton2014).

In dairy animals less than 6 months of age, lung ultrasound can rapidly and easily detect the non-aerated or consolidated lung lesions associated with bacterial pneumonia (Ollivett and Buczinski, Reference Ollivett and Buczinski2016). Depending on the study and regardless of the clinical state of the calf, the sensitivity and specificity of lung ultrasound ranges from 79 to 94% and 94 to 100%, respectively (Rabeling et al., Reference Rabeling, Rehage, Dopfer and Scholz1998; Buczinski et al., Reference Buczinski, Ollivett and Dendukuri2015; Ollivett et al., Reference Ollivett, Kelton, Nydam, Duffield, Leslie, Hewson and Caswell2015). In addition, there is a high correlation (r = 0.92) between the amount of consolidated lung identified on lung ultrasound and gross post-mortem examination (Ollivett et al., Reference Ollivett, Hewson, Schubotz and Caswell2013) which means we can use this tool to measure the severity of pneumonia in the live calf. Ultrasonographic lung lesions in dairy calves are associated with reduced preweaning ADG (Cramer and Ollivett, Reference Cramer and Ollivett2019), increased mortality (Buczinski et al., Reference Buczinski, Forte, Francoz and Bélanger2014), and less milk production during the first lactation (Dunn et al., Reference Dunn, Ollivett, Renaud, Leslie, LeBlanc, Duffield and Kelton2018).

Three BRD subtypes (Ollivett and Buczinski, Reference Ollivett and Buczinski2016; Cramer and Ollivett, Reference Cramer and Ollivett2019) can be defined when a systematic clinical scoring system, such as the Wisconsin Respiratory Score (McGuirk and Peek, Reference McGuirk and Peek2014) is incorporated alongside lung ultrasound: (1) upper respiratory tract infections, (2) clinical pneumonia, and (3) subclinical pneumonia. Although the distributions of BRD subtypes will vary from farm to farm, we have found that at least 1/3 of new cases are subclinical and that for every case of existing clinical respiratory disease, we can expect to find two to four cases of subclinical disease (Ollivett and Buczinski, Reference Ollivett and Buczinski2016; Binversie et al., Reference Binversie, Ruegg, Combs and Ollivett2020).

For these reasons, lung ultrasound combined with clinical respiratory scoring has become the primary way that we monitor the presence of disease, the competency of farm staff for detecting sick calves, and the treatment response on local commercial dairies as well as research projects (Ollivett and Buczinski, Reference Ollivett and Buczinski2016; Holschbach et al., Reference Holschbach, Raabis and Ollivett2019; Binversie et al., Reference Binversie, Ruegg, Combs and Ollivett2020). With regard to measuring the treatment response, once treatment has been initiated, the numbers of live bacteria within the lung are significantly reduced and the draw for new neutrophils into the airway slows down. Neutrophils within the airways will undergo apoptosis within 1–2 days of arrival, and that fibrin and cellular debris will be expelled from the airway through coughing and other cellular mechanisms within 7–10 days (Caswell and Williams, Reference Caswell, Williams and Maxie2016). This phenomenon can be observed ultrasonographically through sequential examinations and lung lesion regression visualized as the airways become aerated again (Holschbach et al., Reference Holschbach, Raabis and Ollivett2019; Binversie et al., Reference Binversie, Ruegg, Combs and Ollivett2020).

Unfortunately, data from recent studies suggest that retreatment rates can be two to three times higher than those reported in the literature (Binversie et al., Reference Binversie, Ruegg, Combs and Ollivett2020); ultrasonographic lung lesions associated with pneumonia initially respond to antibiotic therapy but often recur or worsen shortly after treatment (Holschbach et al., Reference Holschbach, Raabis and Ollivett2019; Binversie et al., Reference Binversie, Ruegg, Combs and Ollivett2020), and that antibiotic treatment does not always result in a bacteriologic cure within the lung despite early treatment and resolution of clinical disease (Holschbach et al., Reference Holschbach, Raabis and Ollivett2019).

More specifically, the common definition for treatment success (rectal temperature < 104°F, normal respiratory pattern, normal attitude; as reviewed by DeDonder and Apley (Reference DeDonder and Apley2015)) used by many manufacturers when establishing efficacy of an antibiotic product, would incorrectly classify 100% of the calves with severe lung disease 5 days after a Mannheimia haemolytica challenge study and 14 days after a Pasteurella multocida challenge (Ollivett et al., Reference Ollivett, Hewson, Schubotz and Caswell2013; Holschbach et al., Reference Holschbach, Raabis and Ollivett2019). These findings indicate that despite early recognition of disease, and judicious antibiotic use, bacterial infection has not resolved at the lung level using on-label treatment regimens. We hypothesize that incomplete bacterial killing along with ineffective innate immune function sets the stage for bacterial replication and relapse or recurrence of consolidation once the antibiotic pressure has been removed. Poor treatment response coupled with misleading clinical criteria for treatment success puts calves at risk for future clinical disease (Binversie et al., Reference Binversie, Ruegg, Combs and Ollivett2020) and prolonged periods of slow growth (Cramer and Ollivett, Reference Cramer and Ollivett2019).

In summary, individual and herd level factors may contribute to treatment failures and ultrasound-guided treatment protocols could re-shape how we measure response to treatment, how we validate dosage regimens for currently approved antimicrobial drugs as well as those drugs undergoing the approval process. Implementing ultrasound-guided treatment protocols on farm should improve calf-level response, result in fewer relapses, decrease duration of disease, thereby improving calf welfare and decreasing cost of disease, ameliorate effect of disease, and ensure that administered antibiotics are effective at establishing a bacteriological cure within the lungs.